Evidence for the butyrate metabolism as key pathway improving ulcerative colitis in both pediatric and adult patients

ABSTRACT

Accumulating evidence has shown many similarities and differences of gene profiles and pathways between pediatric and adult ulcerative colitis (UC) patients. In this study, we aimed to investigate the shared genes and pathways in intestinal tissues of pediatric and adult UC. Differentially expressed genes (DEGs) between pediatric and adult UC were identified via bioinformatic analysis of Gene Expression Omnibus datasets GSE87473 and GSE126124. Gene Ontology and pathway enrichment were used to analyze overlapped and distinguished DEGs. Gene Set Variation Analysis (GSVA) was utilized for contrast consistency. Mice colitis models were induced by dextran sulfate sodium (DSS) and Citrobacter rodentium. 2616 DEGs were screened out in intestinal tissues of adult UC compared with those of adult healthy controls, and 1195 DEGs in pediatrics. Same pathways between pediatric and adult UC were enriched using overlapped DEGs, mainly related to immune responses and metabolic processes, including butyrate metabolism, which was also identified by GSVA analysis. Of note, butyrate metabolism was the exclusive down-regulated pathway enriched by these two analyses, indicating that butyrate metabolism is one of the key pathways associated with both pediatric and adult UC. In addition, butyrate suppressed DSS-induced and Citrobacter rodentium-induced intestinal inflammation in mice. Therefore, the study revealed that butyrate metabolism was critical in both pediatric and adult UC. And butyrate suppressed colitis in mice, which provided a theoretical basis for the potential treatment of butyrate for UC patients.

Abbreviations: UC, Ulcerative colitis; IBD, Inflammatory bowel disease; DEGs, Differentially expressed genes; GEO, Gene Expression Omnibus; SVA, Spatial variant apodization; LIMMA, Linear models for the microarray data; FC, Fold change; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; GSVA, Gene Set Variation Analysis; MSigDB, Molecular Signatures Database; WT, Wild-type; DSS, Dextran sulfate sodium; HC, Healthy control; SD, Standard deviation; SNHG5, Small nucleolar RNA host gene 5; GLP-2, Glucagon-like peptide 2; GSE, Gene set enrichment; ECM, Extracellular matrix; TCA, Tricarboxylic acid cycle; NA, Not available.

KEYWORDS:

• Butyrate
• ulcerative colitis
• pediatric
• adult
• bioinformatic

Research highlights

• Shared genes and pathways in intestinal tissues of pediatric and adult UC were explored.

• Butyrate metabolism was critical in association with both pediatric and adult UC.

• Butyrate suppressed colitis in mice models.

• The study provided a theoretical basis for the potential treatment of butyrate for UC patients.

Acknowledgements

We acknowledge the generous support of the Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University. This work was supported by the National Natural Science Foundation of China (Grant/Award number: 82070565, 81870389); Guangdong Provincial Bio-engineering Research Center for Gastroenterology Diseases; the Science and Technology Planning Project of Guangdong Province (Grant/Award number: 2017B020209003). We thank Sarun Juengpanich and Win Topatana, who are English native speakers in Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China, for revising and polishing our manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

Zheng Zhou and Mingsong Li designed and conducted the analysis. Zheng Zhou, Jiasheng Cao, and Xiaoming Liu wrote the manuscript. Mingsong Li revised the munascript. All authors read and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed here.

Availability of data and material

The datasets used and/or analyzed during this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant/Award number: 82070565, 81870389); Guangdong Provincial Bio-engineering Research Center for Gastroenterology Diseases; the Science and Technology Planning Project of Guangdong Province (Grant/Award number: 2017B020209003).